Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA 91101, USA.
Cancer Causes Control. 2013 Sep;24(9):1615-41. doi: 10.1007/s10552-013-0249-2.
We conducted a systematic review to summarize current evidence on the prognostic utility of DNA methylation markers in prostate cancer and ascertain knowledge gaps to inform future research.
We identified relevant studies using combined key search against PubMed database. Inclusion criteria were studies of human subjects that examined the association between DNA methylation markers and prostate cancer disease outcomes. The methodological quality of each study was systematically evaluated. Findings were qualitatively summarized. Due to heterogeneity and concerns of internal validity, no meta-analysis was performed.
Twenty studies were reviewed; sample size ranged from 35 to 605 men in the prognostic analyses. Sixteen studies examined methylation markers in prostate cancer tissue and four examined circulating DNA methylation markers. Of all genes reviewed, paired-like homeodomain transcription factor 2 (PITX2) methylation was examined in two more rigorously designed studies and was found to be associated with biochemical recurrence. Common limitations in current literature included small sample sizes,lack of adequate adjustment for established prognostic factors, and poor reporting quality.
Evidence on the prognostic utility of methylation markers in prostate cancer is inconclusive. Future research should ascertain large samples with adequate follow-up and include patients of racial/ethnic minority and those treated with modalities other than prostatectomy(e.g., using prostate cancer diagnostic biopsy as tissue source).
我们进行了系统评价，总结了目前关于前列腺癌中 DNA 甲基化标志物预后效用的证据，并确定了知识空白，以指导未来的研究。
我们使用组合关键搜索对 PubMed 数据库进行了相关研究的识别。纳入标准为研究人类受试者，检验 DNA 甲基化标志物与前列腺癌疾病结局之间的关联。系统评估了每个研究的方法学质量。定性总结了研究结果。由于存在异质性和内部有效性的担忧，因此未进行荟萃分析。
共综述了 20 项研究；预后分析中样本量范围为 35 至 605 名男性。16 项研究检测了前列腺癌组织中的甲基化标志物，4 项研究检测了循环 DNA 甲基化标志物。在所有被审查的基因中，成对样同源结构域转录因子 2（PITX2）的甲基化在两项设计更为严谨的研究中进行了检测，并且与生化复发相关。目前文献中的常见局限性包括样本量小、缺乏对既定预后因素的充分调整以及报告质量差。
关于前列腺癌中甲基化标志物预后效用的证据尚无定论。未来的研究应确定具有足够随访的大样本，并包括种族/民族少数群体的患者和接受前列腺切除术以外的治疗方式（例如，使用前列腺癌诊断性活检作为组织来源）的患者。
